Vial system and method for processing liquid-based specimens

ABSTRACT

A vial-based system and method for handling and processing specimens of particulate matter-containing liquid directly in the vial. A processing assembly, which includes a stirrer and a particulate matter separation chamber, is releasably coupled to the inside of the vial cover. The processing assembly remains with the cover when the vial is opened to insert a specimen therein. Application of a particular external force to the closed vial detaches the processing assembly from the cover so that it remains in the vial, for access by automated or manual laboratory equipment, when the cover is subsequently removed.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. provisional application No.60/330,092, filed Oct. 19, 2001, which is incorporated herein byreference. This application also is related to commonly owned U.S.provisional application No. 60/372,080, filed Apr. 15, 2002, and alsoincorporated herein by reference.

BACKGROUND

The present invention is directed to an apparatus and a method forcollecting and processing specimens of biological fluid, includingcollecting uniform layers of cells therefrom suitable for use incytology protocols.

In a wide variety of technologies, the ability and/or facility inseparating matter, typically particulate matter, from a fluid is acritical component in the ability to test for the presence of substancesin the fluid. Too often, interference associated with sample preparationobscures the target particles to such a degree that the process is notsufficiently reliable, or too costly. Such problems exist in variousfields of examination which involve detection and/or diagnosis,including environmental testing, radiation research, cancer screeningthrough cytological examination, microbiological testing, and hazardouswaste contamination, to name just a few.

Cytological examination of a sample begins with obtaining specimensincluding a sample of cells from the patient, which can typically bedone by scraping or swabbing an area, as in the case of cervicalsamples, or by collecting body fluids, such as those obtained from thechest cavity, bladder, or spinal column, or by fine needle aspiration orfine needle biopsy. In a conventional manual cytological preparation,the cells in the fluid are then transferred directly onto a glass slidefor viewing. In a conventional automated cytological preparation, afilter assembly is placed in the liquid suspension and the filterassembly both disperses the cells and captures the cells on the filter.The filter is then removed and placed in contact with a microscopeslide.

In all of these endeavors, a limiting factor in the sample preparationprotocol is adequately separating solid matter from its fluid carrier,and in easily and efficiently collecting and concentrating the solidmatter in a form readily accessible to microscopic examination.Diagnostic microbiology and/or cytology, particularly in the area ofclinical pathology, bases diagnoses on a microscopic examination ofcells and other microscopic analyses. The accuracy of the diagnosis andthe preparation of optimally interpretable specimens typically dependsupon adequate sample preparation. In this regard the ideal specimenwould consist of a monolayer of substantially evenly spaced cells. Newermethodologies such as immunocytochemistry and image analysis requirepreparations that are reproducible, fast, biohazard-free andinexpensive.

Currently, biological samples are collected for cytological examinationsusing special containers. These containers usually contain apreservative solution for preserving the cytology specimen duringshipment from the collection site to the cytology laboratory. Further,cytology specimens collected from the body cavities using a swab, smear,spatula or brush are also preserved in special containers with fixatives(e.g., alcohol or acetone fixatives) prior to transferring cells ontothe slide or membrane for staining or examination.

Specimen containers are known that allow a liquid-based biologicalspecimen to be processed directly in the container so as to obtain asubstantially uniform layer of cells on a collection site (in a filterhousing defining a particulate matter separation chamber) that isassociated with the container itself. See, for example, U.S. Pat. Nos.5,301,685; 5,471,994; 6,296,764; and 6,309,362, all of which areincorporated herein by reference. However, these types of specimencontainers require specially configured apertured covers and adapterstherefor that are designed to mate with the filter housing, and withsuction equipment (e.g., a syringe or a mechanized vacuum source) usedto aspirate liquid from the container and draw it through the filter.Further, extraction of the filter so that it can be pressed against amicroscope slide to transfer collected cells to the slide requiresdisassembly of the cooperating parts of the cover and/or adaptersassociated therewith. If the processing is done by automated equipment,special handling devices are required to carry out such disassembly. Allof this complexity adds time and material and labor cost to theprocessing required prior to the actual cytology examination.

SUMMARY OF THE INVENTION

The present invention concerns a specimen vial that houses a completeprocessing assembly, typically one for stirring the liquid-basedspecimen therein and for holding a filter on which a uniform layer ofcells can be collected from the specimen. It is expected that thespecimen vial would be prepackaged with a liquid preservative solution,as is commonplace.

The processing assembly is coupled to a simple cover for the vial bymeans of a simple and inexpensive releasable coupling. When the cover isremoved at the point-of-care site (doctor's office, clinic, hospital,etc.), the processing assembly remains with the cover to allow medicalpersonnel easy access to the container interior for insertion of abiological specimen into the vial. The cover, along with the attachedprocessing assembly, is then replaced to seal the vial. The vial maythen be sent to a laboratory for processing.

When the vial is manipulated in a simple way while still closed, theprocessing assembly detaches from the cover and remains in the vial foraccess by automated or manual laboratory equipment when the cover issubsequently removed. In a preferred embodiment, a downward force on thecenter of the cover is all that is required to detach the processingassembly from the cover. In contrast with the prior art specimen vialsdiscussed above, the vial of the present invention requires no furtherinteraction with the cover, which can be removed by a simple uncappingdevice and is discarded to avoid contamination.

Accordingly, a first aspect of the invention concerns a method forprocessing particulate matter-containing liquid in a vial comprising acontainer having an opening at its upper end, a cover removably coupledto the container to close the opening, and a processing assemblyreleasably coupled to the cover. The method comprises the steps ofdetaching the processing assembly from the cover while the cover is onthe container, removing the cover to expose the detached processingassembly in the container, and manipulating the processing assembly soas to process the particulate matter-containing liquid in the container.The detaching step comprises applying an external force to the closedvial. The external force may be applied to the central portion of thecover to deflect the cover inwardly.

The processing assembly may comprise a dispersing element, and themanipulating step may comprise moving at least the dispersing element todisperse the particulate matter in the liquid. The dispersing elementmay be rotated to stir the liquid. Before such rotation, the dispersingelement may first be lifted slightly to insure clearance between theprocessing assembly and the container.

The processing assembly may comprise a particulate matter separationchamber at the upper portion thereof adapted to hold a filter assembly,and a tube communicating with the separation chamber and extendingdownwardly therefrom. With such an arrangement the manipulating step maycomprise placing a filter assembly in the separation chamber, sealingthe separation chamber, and applying a vacuum to the separation chamberto draw the stirred particulate matter-containing liquid upwardlythrough the tube and into contact with the filter assembly so as tocollect particulate matter on a surface of the filter assembly. Then thefilter assembly may be removed from the separation chamber, and theparticulate matter collected on the filter assembly contacted with aslide so as to transfer collected particulate matter to the slide.

Another aspect of the invention concerns a vial for holding andprocessing particulate matter-containing liquid. The vial comprises acontainer having an opening at its upper end, a cover removably coupledto the container to close the opening, and a processing assemblyreleasably coupled to the cover so as to be removable from the containerwith the cover while still coupled thereto, and selectively detachablefrom the cover while the cover is on the container so as to remain inthe container when the cover is subsequently removed.

The releasable coupling between the cover and the processing assemblymay comprise mating couplers, respectively carried by the inside of thecover and the upper portion of the processing assembly, that are heldtogether by a retention force and disengage upon application of anexternal force to the vial that overcomes the retention force. Thecouplers may mate and disengage by relative motion in the axialdirection, i.e., parallel to the central axis of the container. Theretention force may be frictional, and the couplers may be press-fittogether.

The couplers may take the form of closely fitting projections, which maybe annular. The upper portion of the processing assembly may comprise abottom wall extending transversely of the container axis, the annularprojection on the processing assembly extending upwardly from the bottomwall to form a cup-shaped recess (which may define a particulate matterseparation chamber adapted to hold a filter assembly). The bottom wallmay have a central hole, in which case a tube communicates with the holeand extends downwardly from the bottom wall. The tube has at least onedispersing element for dispersing particulate matter in the liquid.

The cover may have a central boss that extends into the cup-shapedrecess when the processing assembly is coupled to the cover, the distalend of the central boss contacting or lying close to the bottom wall.When an external force is applied to the central portion of the cover soas to deflect the cover inwardly, the central boss presses against thebottom wall and pushes the bottom wall and the annular projectionthereon away from the cover. The annular projection on the bottom wallmay fit within the annular projection on the cover, so the externalforce deflects the annular projection on the cover outwardly, away fromthe annular projection on the bottom wall.

Yet another aspect of the invention concerns a vial for holding andprocessing particulate matter-containing liquid. The vial comprises acontainer having an opening at its upper end, a cover removably coupledto the container to close the opening, and a processing assembly whollywithin the container and engageable by an external manipulator after thecover is removed. The container has a central axis extending lengthwisethereof through the opening, and a wall surrounding the axis. A portionof the surrounding container wall below the opening supports theprocessing assembly when it is not engaged by a manipulator such thatthe upper portion of the processing assembly is disposed near theopening.

The supporting portion of the container wall may comprise at least threespaced inwardly extending supports on which the processing assemblyrests. These supports may comprise ribs (preferably four) that extendlengthwise of the container.

The processing assembly may comprise a particulate matter separationchamber at the upper portion thereof adapted to hold a filter assembly,a tube communicating with the separation chamber and extendingdownwardly therefrom, and a dispersing element carried by the tube. Theupper portion of the processing assembly has a peripheral portion thatlies close to the surrounding wall and rests on the ribs. The processingassembly may be rotated about the central axis so as to cause thedispersing element to stir the particulate matter-containing liquid, theprocessing assembly being dimensioned to rotate freely in the containerwithout contacting the surrounding wall when lifted slightly off theribs by a rotating manipulator. The close-fitting peripheral portion ofthe processing assembly prevents liquid from splashing out of thecontainer during stirring, thus minimizing biohazard exposure. The ribsaid in the dispersion of particulate matter in the liquid.

BRIEF DESCRIPTION OF THE DRAWING FIGURES

A preferred embodiment that incorporates the best mode for carrying outthe invention is described in detail below, purely by way of example,with reference to the accompanying drawing, in which:

FIG. 1 is a vertical sectional view through a specimen vial according tothe invention, showing the processing assembly in the vial coupled tothe cover;

FIG. 2 a is a front elevational view of the container portion of thevial;

FIG. 2 b is a top plan view of the container, shown with the processingassembly removed;

FIG. 3 is a top plan view of the processing assembly;

FIG. 4 is a bottom plan view of the liner that fits within the cover;

FIG. 5 is an exploded vertical sectional view of the processing assemblyand a filter assembly adapted for use in the processing assembly;

FIG. 6 is a vertical sectional view of the upper portion of theprocessing assembly, showing the filter assembly in place in theparticulate matter separation chamber and engaged by a suction head;

FIG. 7 is a partial schematic view of the arrangement depicted in FIG.6, showing the flow of liquid and particulate matter separatedtherefrom;

FIG. 8 is a vertical sectional view of the specimen vial similar to FIG.1, but showing the processing assembly detached from the cover;

FIGS. 9-13 are vertical sectional views of a container according to theinvention undergoing various stages of automated laboratory handling, asfollows:

FIG. 9 shows uncapping of the container (cover removal);

FIG. 10 shows primary stirring of the specimen;

FIG. 11 shows placement of a filter in the particulate matter separationchamber of the processing assembly;

FIG. 12 shows acquisition of a specimen on the filter by aspiration ofliquid through the processing assembly;

FIG. 13 shows removal of the filter and transfer of the specimen to amicroscope slide; and

FIG. 14 is a top plan view of an automated apparatus for handling vialsaccording to the invention and carrying out the specimen processingsteps illustrated in FIGS. 9-13.

It is to be understood that the invention is not limited in itsapplication to the details of construction and the arrangement ofcomponents of the preferred embodiment described below and illustratedin the drawing figures. Further, while the preferred embodiment isdisclosed as primarily useful in the collection and processingbiological fluids for cytology examination, it will be appreciated thatthe invention has application in any field in which samples ofparticulate matter are to be prepared from a liquid that contains suchparticulate matter.

DETAILED DESCRIPTION

Referring to FIGS. 1, 2 a and 2 b, a vial 10 according to the inventioncomprises a container 20, a cover 30 and a processing assembly 40.Container 20 is molded of plastic, preferably polypropylene, and has asubstantially cylindrical wall 21, surrounding its longitudinal axis,joined to a conical bottom wall 22. A small portion 24 of wall 21 isflat, the outer surface of the flat portion adapted to receive indicia,e.g., a bar code label, containing information concerning the specimenplaced in the vial. Although only one flat portion is shown, thecontainer could be configured with two or more flat portions, eachadapted to receive indicia. The bottom end of flat portion 24 has anarcuate notch 25 which acts to keep the container in a properorientation when handled by automated laboratory processing equipmentdesigned to cradle the container and move it through various processingstations. Four longitudinal ribs 26 project inwardly from wall 21. Theupper ends 27 of ribs 26 form rests for the processing assembly 40 whenit is detached from cover 30 (see FIG. 8). The top of container 20 hasan opening 28 and a standard right-hand helical thread 29 thatpreferably extends for one and one half turns and mates with a similarthread on cover 30. Other types of cover-to-container coupling may beused, such as a bayonet coupling, snap-fit arrangement, etc.

Cover 30 comprises a commercially available simple molded plasticthreaded cap 31, and a novel liner 32 retained in the cap. Cap 31 has aflat solid top, and an externally knurled depending flange with aninternal helical thread 33 that mates with thread 29 on container 20.Referring to FIG. 4, liner 32 is molded of plastic material, preferablypolyethylene, and has a substantially flat base 34 sized to fit snuglywithin cap 31, behind thread 33, so that the liner is not readilyseparated from the cap. As seen in FIG. 1, liner base 34 serves as aseal between the cap 31 and the rim of the container wall 21.

Liner base 34 has a coupler in the form of an annular projection 35 thatpreferably is slightly conical in shape, preferably forming an angle ofabout 5° to its central axis. In other words, the inner diameter ofannular coupler 35 is greater at its proximal end, where it joins linerbase 34, than at its distal end. Liner base 34 also has a centralannular boss 36 that projects further from base 34 than annular coupler35 so as to interact with processing assembly 40, as described below.While the use of a separate liner mated to a standard cap is preferred,the cover could be integrally molded in one piece to include the annularcoupler 35 and the central annular boss 36.

Referring to FIGS. 1, 3 and 5, processing assembly 40 is in the form ofa stirrer molded of plastic, preferably polypropylene, having a circularbase or bottom wall 41, sloped at its center, with a central inlet port42; a central depending suction tube 43 with two diametrically opposedsuction ports 44 near the bottom of the tube; and a dispersing elementin the form of laterally extending vanes 45. The upper portion of thestirrer 40 has a cup-shaped particulate matter separation chamber ormanifold 46 defined by base 41 and an upstanding annular wall 47. Theupper edges of wall 47 are beveled, the inner edge 48 preferably beingbeveled to a greater degree to facilitate placement of a filter assemblyF in manifold 46, as described below.

Annular wall 47 serves as a coupler for releasably coupling the stirrer40 to cap liner 32, and is therefore dimensioned to fit snugly withinannular coupler 35 (see FIG. 1). Specifically, there is a friction orpress fit between couplers 35 and 47 such that normal handling of theclosed vial, and normal handling of cover 30 when removed from container20 (e.g., to place a biological specimen in the container) will notcause separation of the stirrer from the cover. Coupler 47 isdimensioned relative to coupler 35 so that there is a very slightinitial diametrical interference, preferably about 0.31 mm. Coupler 47is stiffer than coupler 35, so assembly of the stirrer to the coverinvolves slight deformation principally of coupler 35, resulting in africtional force that keeps the stirrer and the cover engaged.Application of an external force to the vial that overcomes thisfrictional retention force will cause stirrer 40 to detach from cover 30and drop by gravity further into container 20 (see FIG. 8).

The external separation force preferably is applied to the centralportion of cover 30 (see the arrow in FIG. 8), which deflects cap 31 andliner 32 inwardly. As illustrated in FIG. 1, central boss 36 on liner 32is dimensioned such that its distal end just contacts or lies very closeto base 41 of the stirrer. Thus, when the central portion of the coveris depressed, central boss 36 will deflect further than annular coupler35 on liner 32 and push stirrer 40 out of engagement with coupler 35.Inward deflection of liner 32 also causes coupler 35 to spreadoutwardly, thereby lessening the retention force and facilitatingdetachment of the stirrer. The separation force applied to cover 30 andrequired to detach the stirrer should be in the range of 10 to 30 lbs.,preferably about 12 lbs.

Another way to detach the stirrer from the cover is to exert an abruptupward external force on the vial, either manually or mechanically(automatically), to yield an acceleration force that overcomes thefrictional retention force and effectively pulls the stirrer out ofengagement with the cover. This can be done by, e.g., moving the closedvial rapidly downwardly to rap the bottom of the container 20 against arather hard surface. Automated vial handling machinery can accomplishthis by, e.g., mechanically and/or pneumatically thrusting the closedvial into the carrier that will hold the vial during the subsequentprocessing steps, or by dropping the vial down a chute into the carriera sufficient distance to dislodge the stirrer. Another way to exert anabrupt upward external force on the vial is to strike the bottom of thecontainer 20 with a striking member. Automated vial handling machinerycan accomplish this by, e.g., cradling the container 20 and momentarilythrusting a striker against the bottom of the container, e.g. through abottom opening in the vial carrier. The design of these and othervariants of suitable automated mechanisms for accomplishing these tasksshould be within the grasp of those skilled in the mechanical arts.

Once detached from the cover 30, stirrer 40 comes to rest on the upperends 27 of ribs 26. See FIG. 8. The particulate matter separationchamber (manifold) 46 thus is stably supported near the containeropening and easily accessed by processing equipment, whether manual orautomatic, which will manipulate the stirrer so as to process thespecimen directly in the container. At least three ribs 26 are requiredto form a stable support for the stirrer, but four are preferred becausethat number seems to promote more thorough dispersion of the particulatematter in the liquid during stirring.

FIG. 14 shows an overview and some details of one form of automated(computer-controlled) device for handling specimen vials according tothe invention. The device is referred to as an “LBP” device (forliquid-based slide preparation), and can be integrated into a completeautomated laboratory system. Further details of the LBP device and thesystem are set forth in the above-referenced concurrently filedprovisional patent application entitled “Automated System and Method forProcessing Multiple Liquid-Based Specimens.”

In the LBP device a conveyor 100 trained around sprockets 102, 104 isdriven stepwise in accordance with a specified operating protocol toadvance specimen vials along a processing path from one operating headto another. Conveyor 100 has thirty vial carriers 106 (numbered 1-30)serially linked by pins 108. Vial carriers 106 are in the form ofreceptacles that are keyed to accept containers 20 in only one position(i.e., keyed to notches 25 in containers 20). Loading of vials intoconveyor 100 can be done manually, or automatically by a pick-and-placeauto loader 110. Unloading of processed containers can be done manually,or by the same or a different pick-and-place auto loader.

After a specimen vial is loaded into a receptacle 106, data concerningthe specimen therein, including the identity of the patient, is firstacquired at a bar code reading station 112. This data governs theparticular operating protocol to be carried out. The vial then moves toan uncapping station 120, where an uncapping head having a leadscrew-driven plunger (not shown) first applies a downward force to thecenter of the cover (see FIG. 8) to dislodge stirrer 40 from the cover,and then grips the knurled rim of the cover (e.g., using a taperedgripping jaw, not shown), twists it counterclockwise to remove thecover, and then discards it. FIG. 9 schematically illustrates the coverremoval step, and shows the stirrer resting on ribs 26 after the coveris removed.

After uncapping the vial moves to a primary stirring station 130 wherehigh-speed stirring is carried out. Here (see FIG. 10) a stirring headcomprising an expanding collet 132 moves downwardly by action of a leadscrew (not shown) into the open upper recess (manifold) 46 of thestirrer 40, and expands against annular wall 47 to grip the stirrer. Thecollet lifts the stirrer very slightly so that it clears the ribs 26,and then spins the stirrer in accordance with the sample-specificstirring protocol as determined by the bar code reader 112. The base orbottom wall 41 of the stirrer acts as a slinger to thrust any liquidthat may rise along the stirrer against the container wall 21, andprevents the escape of liquid from the container. When stirring iscomplete, the collet 132 releases the stirrer and rises to clear thecontainer so that it can move on.

At the next station 140 a filter assembly F is loaded into theparticulate matter separation chamber (manifold) 46 at the upper end ofthe stirrer. See FIG. 11. The filter assembly is dispensed by a leadscrew-driven pusher 142 from a magazine 144 having eight filter tubes146 which can house filters of different types. The filter dispensed isdetermined by the specimen-specific processing protocol.

After a filter assembly F is loaded the vial moves to a specimenacquisition station 150. Here a suction head 152 (see FIG. 12) descendsby operation of a lead screw (not shown) to engage the upper portion ofthe stirrer 40. The suction head has an O-ring 153 that seals againstthe outside of annular wall 47, and two concentric O-rings 154, 155 thatseal against the top of filter assembly F. An inner suction line 156draws a vacuum on filter F, in accordance with the specimen-specificprocessing protocol, to aspirate particulate matter-containing liquidfrom the container through suction tube 43, into the particulate matterseparation chamber (manifold) 46 and through the filter assembly F,leaving a monolayer of cells on the bottom surface of the filter asdescribed below. Prior to aspiration the specimen may be stirred again,this time more slowly, to re-suspend the particulate matter in theliquid. This is done by the rotatably mounted suction head 152, which isturned by a timing belt 151.

When aspiration of the specimen is complete, the suction head 152 israised. The inner portion 158 of the suction head is extended at thesame time by action of a pneumatic cylinder (not shown). As the suctionhead 152 is raised, the outer portion 157 of the suction head disengagesfrom the stirrer 40 (see FIG. 13), but the filter assembly F is retainedon the inner portion 158 of the suction head by application of vacuumthrough suction line 159 to the annular space between O-rings 154 and155. Thus the suction head 152 removes filter assembly F from thestirrer, and can continue to apply light suction via suction line 156through the filter to effect a desired degree of moisture control of thecellular material on the filter. The suction head 152 then pivots aboutan axis 161 (see FIG. 14) to position the filter over a microscope slideS delivered from a slide cassette 162 at a slide presentation station160. The suction head then moves downwardly to press the filter againstthe slide S and transfer the monolayer of cells thereto. The phantomlines in FIG. 13 show this change in position of suction head 152 andcontact of the filter with slide S. A few drops of liquid fixative arethen applied to the specimen on the slide, and the slide is shuttledback to its original position in the slide cassette.

After the specimen has been acquired, the container moves to a recappingstation 170 where a new cap, e.g., a heat-sealed foil, is applied toseal the container.

FIG. 6 shows some details of the filter assembly F and its functionalcooperation with the stirrer manifold 46 and the inner portion 158 ofsuction head 152. Filter assembly F comprises a filter holder 200 thataccommodates a filter 202. Filter 202 comprises a porous frit 203 and afilter membrane 205 that lies over the lower surface of the frit 203 andis sealed to the periphery of holder 200, e.g., by sonic welding. Thereis a single, central opening 204 in the top of filter holder 200. Thefilter 202 (and hence the entire filter assembly F) is supported at itsperiphery on stirrer base 41 by an array of ribs 48 a that definebetween them radial flow passages 49 (see FIG. 3). The O-rings 154, 155of inner suction head portion 158 seal against the top of filter holder200. Suction applied through port 156 creates a vacuum around centralopening 204 and within the filter holder 200, which draws liquid intothe separation chamber (manifold) 46 and through the filter 202. Theflow is vertical through the filter and also across the filter membraneface because of the radial flow passages 49. See FIG. 7, which showsparticulate matter (cells) as circles and indicates the flow by arrows.This dual-flow configuration promotes the formation of a monolayer ofcells on the filter. See, e.g., the aforementioned U.S. Pat. No.5,471,994, which describes this dual-flow concept in general. The slopedbottom wall 41 of the manifold 46 further promotes the formation of amonolayer of cells. The constructional details of the filter assemblyand its cooperation with the sloped-bottom manifold 46 are set forth inthe aforementioned concurrently filed provisional patent applicationentitled “Automated System and Method for Processing MultipleLiquid-Based Specimens.”

The invention thus provides an efficient, inexpensive, convenient andsafe vial-based system and method for collecting, handling andprocessing biological specimens and other specimens of particulatematter-containing liquid. It is ideally suited for use in automatedequipment that provides consistently reliable processing tailored tosample-specific needs. Should the stirrer inadvertently become detachedfrom the cover at the point-of-care site, the physician simply placesthe stirrer loosely in the vial so that it descends into the specimenand then screws the cover on as usual. This is not difficult because theribs in the vial allow insertion of the stirrer in only one direction.Once the vial is closed with the specimen inside, the stirrer remains inthe vial throughout processing and is sealed therein when the vial isre-capped.

Various modifications will be apparent to those skilled in the artwithout departing from the scope of the invention, which is defined bythe appended claims.

1. A vial for holding and processing particulate matter-containingliquid, comprising: a container having an opening at its upper end; animperforate cover removably coupled to the container to close theopening; and a processing assembly that is separate from the containerand is coupled to the cover, proximate the interface between the coverand the opening, by a releasable coupling that allows the processingassembly to be removed from the container with the cover while stillcoupled thereto, and is configured to allow the processing assembly tobe selectively detached inwardly from the cover while the cover is onthe container so that the processing assembly remains in the containerwhen the cover is subsequently removed; wherein the releasable couplingbetween the cover and the processing assembly comprises mating couplers,respectively carried by the inside of the cover and an upper portion ofthe processing assembly, that are held together by a retention force anddisengage upon application of an external force to the vial thatovercomes the retention force; wherein the container has a central axisextending lengthwise of the container through the opening, and thecouplers mate and disengage by relative motion in the axial direction;wherein the retention force is frictional; wherein the couplers arepress-fit together; and wherein the couplers comprise closely fittingprojections.
 2. A vial according to claim 1, wherein the projections areannular.
 3. A vial according to claim 2, wherein the upper portion ofthe processing assembly comprises a bottom wall extending transverselyof the axis, the annular projection on the processing assembly extendingupwardly from the bottom wall to define a cup-shaped recess.
 4. A vialaccording to claim 3, wherein the bottom wall has a central hole, and atube communicates with the hole and extends downwardly from the bottomwall.
 5. A vial according to claim 4, wherein the tube has at least onedispersing element for dispersing particulate matter in the liquid.
 6. Avial according to claim 3 or claim 5, wherein the cover has a centralboss that extends into the cup-shaped recess when the processingassembly is coupled to the cover, the distal end of the central bosscontacting or lying close to the bottom wall.
 7. A vial according toclaim 6, wherein the external force is applied to the central portion ofthe cover so as to deflect the cover inwardly to press the central bossagainst the bottom wall and push the bottom wall and the annularprojection thereon away from the cover.
 8. A vial according to claim 7,wherein the annular projection on the bottom wall fits within theannular projection on the cover, and the external force deflects theannular projection on the cover outwardly, away from the annularprojection on the bottom wall.
 9. A vial according to claim 1, whereinthe container wall surrounding the processing assembly supports theprocessing assembly when it is detached from the cover so as to keep theprocessing assembly from resting on the bottom of the container.
 10. Avial according to claim 9, wherein the container wall has at least threespaced inwardly extending supports on which the processing assemblyrests when it is detached from the cover.
 11. A vial according to claim10, wherein the inwardly extending supports comprise ribs that extendlengthwise of the container.
 12. A vial according to claim 11,comprising four ribs.
 13. A vial according to claim 1, wherein thecoupler carried by the inside of the cover is on a liner retained in thecover.
 14. A vial according to claim 1, wherein the liner has a centralboss that extends inwardly toward the processing assembly, and whereinthe external force is applied to the central portion of the cover so asto deflect the cover and the liner inwardly to press the central bossagainst the processing assembly and push the processing assembly awayfrom the cover.
 15. A vial according to claim 13 or claim 14, whereinthe liner serves as a seal between the cover and the container.
 16. Avial for holding and processing particulate matter-containing liquid,comprising: a container having an opening at its upper end, a centralaxis extending lengthwise of the container through the opening, and awall surrounding the axis; a cover removably coupled to the container toclose the opening; and a processing assembly separate from and whollywithin the container and engageable by an external manipulator after thecover is removed, wherein a portion of the surrounding container wallbelow the opening loosely supports the processing assembly when it isnot engaged by a manipulator such that an upper portion of theprocessing assembly is disposed near but not above the opening; whereinthe supporting portion of the container wall comprises at least threespaced inwardly extending supports on which the processing assemblyrests; wherein the processing assembly comprises a particulate matterseparation chamber at the upper portion thereof adapted to hold a filterassembly, a tube communicating with the separation chamber and extendingdownwardly therefrom, and a dispersing element carried by the tube, theupper portion of the processing assembly having a peripheral portionthat lies close to the surrounding wall and rests on the supportingportion of the surrounding wall.
 17. A vial according to claim 16,wherein the inwardly extending supports comprise ribs that extendlengthwise of the container.
 18. A vial according to claim 17,comprising four ribs.
 19. A vial for holding and processing particulatematter-containing liquid, comprising: a container having an opening atits upper end, a central axis extending lengthwise of the containerthrough the opening, and a wall surrounding the axis; a cover removablycoupled to the container to close the opening; and a processing assemblyseparate from and wholly within the container and engageable by anexternal manipulator after the cover is removed, wherein a portion ofthe surrounding container wall below the opening loosely supports theprocessing assembly when it is not engaged by a manipulator such that anupper portion of the processing assembly is disposed near but not abovethe opening; wherein the processing assembly comprises a particulatematter separation chamber at the upper portion thereof adapted to hold afilter assembly, a tube communicating with the separation chamber andextending downwardly therefrom, and a dispersing element carried by thetube, the upper portion of the processing assembly having a peripheralportion that lies close to the surrounding wall and rests on thesupporting portion of the surrounding wall; wherein the processingassembly is rotatable about the central axis so as to cause thedispersing element to stir the particulate matter-containing liquid, theprocessing assembly being dimensioned to rotate freely in the containerwithout contacting the surrounding wall when lifted slightly off thesupporting portion of the surrounding wall by a rotating manipulator;wherein the supporting portion of the container wall comprises at leastthree spaced inwardly extending supports on which the peripheral portionof the processing assembly rests.
 20. A vial according to claim 19,wherein the inwardly extending supports comprise ribs that extendlengthwise of the container and aid in the dispersion of particulatematter in the liquid when the processing assembly is rotated.
 21. A vialaccording to claim 20, comprising four ribs.
 22. A vial according toclaim 16, wherein the processing assembly is movable relative to thesurrounding container wall.
 23. A vial according to claim 22, whereinthe processing assembly is rotatable about the central axis and isdimensioned to rotate freely in the container substantially withoutcontacting the surrounding wall when lifted slightly off the supportingportion of the surrounding wall by a rotating manipulator.